In Phase I of this award I will obtain a Ph.D. in physiology investigating autonomic regulation of horse airways. Our laboratory is presently studying airway reactivity in a group of ponies with spontaneously occurring airway disease and in a group of normal ponies. Studies of mechanisms of disease are hampered by lack of knowledge of autonomic innervation and function of the tracheobronchial smooth muscle. Autonomic function will be studied in vivo and in vitro. In vivo pulmonary resistance dynamic and static compliance will be measured during vagal stimulation at a range of frequencies and voltages after adrenergic blockade. Sympathetic stimulation will be achieved with dimethylphenylpiperazinium (DMPP) after cholinergic blockade. Adrenalectomy and use of DMPP will allow determination of adrenergic receptors stimulated by circulating catecholamines and those stimulated by sympathetic nerves. In vitro, trachealis muscle strips and bronchial rings from three generations of bronchi will be suspended in organ baths. Response to field electrical stimulation in the presence of appropriate blockers will determine the presence and function of sympathetic and parasympathetic innervation at differing levels of the tracheobronchia tree. Responses to electrical stimulation will be compared to responses to adrenergic and cholinergic agonists to compare receptors accessible to nerve stimulation and those accessible to circulating agonists. These two series of experiments will determine autonomic distribution in pony airways. Phase II experiments will investigate interactions of airay epithelium with bronchial smooth muscle. Responses to field electrical stimulation and autonomic agonists will be compared in adjacent muscle strips and bronchial rings with and without epithelium. These experiments will be conducted in airways from normal ponies and those with chronic airway disease. By use of "epithelial sandwiches" I will determine if factors produced by normal and diseased epithelium modulate smooth muscle function. Crossover experiments will apply "diseased" epithelium to "normal" muscle and "normal" epithelium to "diseased" muscle.